Objective: Radiation-induced skin injury remains a serious concern for radiation therapy. Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme catabolism, has been reported to have potential antioxidant and anti-apoptotic properties. However, the role of HO-1 on radiation-induced skin damage remains unclear. This study aims to elucidate the effects of HO-1 on radiation-induced skin injury in rats. Methods: A control adenovirus (Ad-EGFP) and a recombinant adenovirus (Ad-HOl-EGFP) were constructed. Rats were irradiated to the buttock skin with a single dose of 45 Gy followed by a subcutaneous injection of PBS, 5 × 109 genomic copies of Ad-EGFP or Ad-HOl-EGFP (n = 8). After treatment, the skin MDA concentration, SOD activity and apoptosis were measured. The expression of antioxidant and pro-apoptotic genes was determined by RT-PCR and real-time PCR. Skin reactions were measured at regular intervals using the semi-quantitative skin injury score. Results: Subcutaneous injection of Ad-HOl-EGFP infected both epidermal and dermal cells, and could spread to the surrounding regions. Radiation exposure upregulated the transcription of the antioxidant enzyme genes, including SOD-1, GPx2 and endogenous HO-1. HO-1 overexpression decreased lipid peroxidation and inhibited the induction of ROS scavenging proteins. Moreover, HO-1 exerted an anti-apoptotic effect by suppressing FAS and FASL expression. Subcutaneous injection of Ad-HOl-EGFP demonstrated significant improvement in radiation-induced injury. Conclusions: The present study provides evidences for the protective role of HO-1 in alleviating radiation-induced skin damage in rats, which is helpful for the development of therapy for radiationinduced skin injury.
Shuyu Zhang Jinchang Wu Chuanjun Song Jundong Zhou Ling Xie Xingjun Pengfei Liu Jianping Cao Xueguang Zhang Wei-Qun Ding
School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, C The Core Laboratory of Suzhou Cancer Center and Department of Radiotherapy of Suzhou Hospital Affili School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, C Department of Gastroenterology, the Affiliated Jiangyin Hospital of Southeast University, Jiangyin 2 School of Radiation Medicine and Protection, Medical College of Soochow University, Suzhou 215123, C Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, 73104,USA